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Emerging treatment options for BRAF-mutant colorectal cancer

Authors Ursem C, Atreya CE, Van Loon K

Received 26 October 2017

Accepted for publication 8 February 2018

Published 22 March 2018 Volume 2018:8 Pages 13—23


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly

Carling Ursem, Chloe E Atreya, Katherine Van Loon

Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA, USA

Abstract: The personalization of cancer care is rooted in the premise that there are subsets of patients with tumors harboring clinically relevant targets for patient-specific treatments. Colorectal cancer (CRC) is a disease that has historically been notable for its dearth of biomarkers that are predictive of response to targeted therapies. In recent years, BRAFV600E-mutated CRC has emerged as a distinct biologic entity, typically refractory to standard chemotherapy regimens approved for the treatment of metastatic CRC and associated with a dismal prognosis. Multiple clinical trials sought to replicate the successes of targeted therapies seen in BRAFV600E-mutated melanoma without success; metastatic BRAFV600E-mutated CRC is clearly a distinct biologic entity. We review a number of recent studies demonstrating the evidence of modest responses to combinations of BRAF, EGFR, and/or MEK inhibition in patients with metastatic BRAFV600E-mutated CRC; however, despite advances, overall survival remains far inferior for these patients compared to their BRAF-wild-type counterparts. Development of combination therapies to impede signaling through the MAPK pathway through alternate targets remains an area of active investigation. Reflecting the rapid evolution of efforts for this small subset of CRC patients, the first-ever Phase III study is now underway evaluating the combination of BRAF, EGFR, and MEK inhibition. Immunotherapies are also an area of active research, particularly for the subset of patients with tumors that are also microsatellite instability (MSI) high. Here, we summarize the current landscape and emerging data on the molecular, clinical, and therapeutic aspects of BRAF-mutant CRC.

Keywords: colon cancer, BRAF mutation, molecular targets, targeted therapy

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